Treatment of infections caused by multidrug-resistant Gram-negative bacteria:Report of the British Society for Antimicrobial Chemotherapy/Healthcare Infection Society/British Infection Association Joint Working Party

The Working Party makes more than 100 tabulated recommendations in antimicrobial prescribing for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) and suggest further research, and algorithms for hospital and community antimicrobial usage in urinary infection. The international definition of MDR is complex, unsatisfactory and hinders the setting and monitoring of improvement programmes. We give a new definition of multiresistance. The background information on the mechanisms, global spread and UK prevalence of antibiotic prescribing and resistance has been systematically reviewed. The treatment options available in hospitals using intravenous antibiotics and in primary care using oral agents have been reviewed, ending with a consideration of antibiotic stewardship and recommendations. The guidance has been derived from current peer-reviewed publications and expert opinion with open consultation. Methods for systematic review were NICE compliant and in accordance with the SIGN 50 Handbook; critical appraisal was applied using AGREE II. Published guidelines were used as part of the evidence base and to support expert consensus. The guidance includes recommendations for stakeholders (including prescribers) and antibiotic-specific recommendations. The clinical efficacy of different agents is critically reviewed. We found there are very few good-quality comparative randomized clinical trials to support treatment regimens, particularly for licensed older agents. Susceptibility testing of MDR GNB causing infection to guide treatment needs critical enhancements. Meropenem- or imipenem-resistant Enterobacteriaceae should have their carbapenem MICs tested urgently, and any carbapenemase class should be identified: mandatory reporting of these isolates from all anatomical sites and specimens would improve risk assessments. Broth microdilution methods should be adopted for colistin susceptibility testing. Antimicrobial stewardship programmes should be instituted in all care settings, based on resistance rates and audit of compliance with guidelines, but should be augmented by improved surveillance of outcome in Gram-negative bacteraemia, and feedback to prescribers. Local and national surveillance of antibiotic use, resistance and outcomes should be supported and antibiotic prescribing guidelines should be informed by these data. The diagnosis and treatment of both presumptive and confirmed cases of infection by GNB should be improved. This guidance, with infection control to arrest increases in MDR, should be used to improve the outcome of infections with such strains. Anticipated users include medical, scientific, nursing, antimicrobial pharmacy and paramedical staff where they can be adapted for local use

SURVEILLANCE OF MULTIDRUG-RESISTANT UROPATHOGENIC ESCHERICHIA COLI IN HOSPITALIZED PATIENTS AND COMMUNITY SETTINGS IN THE SOUTH OF LEBANON

Urinary Tract Infection (UTI) is one of the common infectious diseases in both hospitals as well as community settings; they are recognized to be among the most serious worldwide bacterial infections impacting 150 million people globally every year. The purpose of this study was to assess the changing antibiotics resistance profile for uropathogenic Escherichia coli isolated from community and hospital setting over a period of time (2018–2019) with a special emphasis on ESBL/MDR producing Escherichia coli. A descriptive retrospective study was conducted among patients with uropathogenic Escherichia coli from both community and hospital settings in south Lebanon. Out of 863 patients with positive uropathogenic Escherichia coli, 451 (52.25 %) comes from the community while 412 (47.74 %) came from the hospital settings. Almost 60.83 % are not Extended Spectrum Beta-Lactamases (ESBL), 31.4 % ESBL, and 7.76 % Multiple drug resistance (MDR). The majority of urinary tract infections are related to the female population (78.21 %). The most vulnerable age for both gender to develop UTI belong to elderly population (\u3e64 years) which account 37.19 % of all isolates. Statistically, we observed a high resistance rate toward all antibiotics using in the treatment of urinary tract infections such as Cefixime (45.30 %), Sulfamethoxazole (44.95 %), Ciprofloxacin (38.23 %) and Augmentin (38.93 %). A statistically significant association was observed between risk factors for hospitalized patients and all age categories with (P \u3c 0.05). Susceptibility profiles are critical to be evaluated in countries such as Lebanon where excessive use of antibiotics is observed at all levels. Therefore, this finding is useful for the determination of appropriate antimicrobial treatment in UTI patients that are caused by Escherichia coli and to follow the antimicrobial stewardship program to reduce the rate of resistance toward antibiotics

Treatment of infections caused by multidrug-resistant Gram-negative bacteria: report of the British Society for Antimicrobial Chemotherapy/Healthcare Infection Society/British Infection Association Joint Working Party

The Working Party makes more than 100 tabulated recommendations in antimicrobial prescribing for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) and suggest further research, and algorithms for hospital and community antimicrobial usage in urinary infection. The international definition of MDR is complex, unsatisfactory and hinders the setting and monitoring of improvement programmes. We give a new definition of multiresistance. The background information on the mechanisms, global spread and UK prevalence of antibiotic prescribing and resistance has been systematically reviewed. The treatment options available in hospitals using intravenous antibiotics and in primary care using oral agents have been reviewed, ending with a consideration of antibiotic stewardship and recommendations. The guidance has been derived from current peer-reviewed publications and expert opinion with open consultation. Methods for systematic review were NICE compliant and in accordance with the SIGN 50 Handbook; critical appraisal was applied using AGREE II. Published guidelines were used as part of the evidence base and to support expert consensus. The guidance includes recommendations for stakeholders (including prescribers) and antibiotic-specific recommendations. The clinical efficacy of different agents is critically reviewed. We found there are very few good-quality comparative randomized clinical trials to support treatment regimens, particularly for licensed older agents. Susceptibility testing of MDR GNB causing infection to guide treatment needs critical enhancements. Meropenem- or imipenem-resistant Enterobacteriaceae should have their carbapenem MICs tested urgently, and any carbapenemase class should be identified: mandatory reporting of these isolates from all anatomical sites and specimens would improve risk assessments. Broth microdilution methods should be adopted for colistin susceptibility testing. Antimicrobial stewardship programmes should be instituted in all care settings, based on resistance rates and audit of compliance with guidelines, but should be augmented by improved surveillance of outcome in Gram-negative bacteraemia, and feedback to prescribers. Local and national surveillance of antibiotic use, resistance and outcomes should be supported and antibiotic prescribing guidelines should be informed by these data. The diagnosis and treatment of both presumptive and confirmed cases of infection by GNB should be improved. This guidance, with infection control to arrest increases in MDR, should be used to improve the outcome of infections with such strains. Anticipated users include medical, scientific, nursing, antimicrobial pharmacy and paramedical staff where they can be adapted for local use

Outcome of sepsis due to Pseudomonas aeruginosa: Impact of antibiotic resistance and therapy

Hintergrund: Pseudomonas aeruginosa zählt zu den häufigsten Ursachen einer gram-negativ bedingten bakteriellen Sepsis. Hohe Mortalitätszahlen sind besonders bei Patienten mit schweren Grunderkrankungen zu verzeichnen. Charakteristisch für das Bakterium ist nicht nur die hohe intrinsiche Antibiotikaresistenz, sondern auch die Fähigkeit zusätzlich Resistenzmechanismen zu erlangen. Die weltweit steigenden Resistenzraten, insbesondere die der multiresistenten Stämme, erschweren eine adäquate Therapie hospitalisierter Patienten. Methodik: Im Rahmen dieser Dissertation wurden die Gesamtmortalität und Risikofaktoren von Patienten mit einer durch das Pseudomonas aeruginosa Bakterium verursachte Sepsis untersucht. Als sekündäre Zielvariabeln wurde die Mortalität in Bezug auf adäquate antimikrobielle Therapie, antimikrobielle Kombinations- bzw. Monotherapie und Multiresistenz (definiert als Resistenz gegen mindestens zwei Pseudomonas-wirksame Antibiotika) untersucht. In die retrospektive Kohortenstudie wurden Patienten eingeschlossen, die sich im Zeitraum Januar 2009 bis Oktober 2015 in stationärer Behandlung am Universitätsklinikum in Tübingen befanden. Es wurden epidemiologische, medizinische und mikrobiologische Daten aus den Patientenakten erhoben und im Rahmen einer Ereigniszeitanalyse wurde das Cox-Regressionsmodell zur uni- und multivariaten Analyse der Daten herangezogen. Ergebnisse: Insgesamt konnten Daten von 104 Patienten mit einer Pseudomonas aeruginosa Blutstrominfektion analysiert werden. Die Gesamtmortalität der Kohorte betrug 37.5 %. Die univariate Analyse zeigte einen signifikanten Zusammenhang zwischen der Mortalität und folgenden Risikofaktoren: Chemotherapie (adjusted HR 2.12 [95% CI 1.0-4.5], p=0.04), Neutropenie (adjusted HR 2.54 [95% CI 1.25-5.18], p=0.01), unbekannte Infektionsquelle (adjusted HR 2.45 [95% CI 1.28-4.69], p=0.006), Multiresistenz (adjusted HR 3.05 [95% CI 1.53-6.08], p=0.001) und inadäquate empirische Antibiotika-Therapie (adjusted HR 2.24 [95% CI 1.12-4.49], p=0.02). Die Gesamtmortalität für Patienten mit einer adäquaten empirischen Monotherapie, einer inadäquaten empirischen Monotherapie, einer adäquaten empirischen Kombinationstherapie und einer inadäquaten empirischen Kombinationstherapie waren wie folgt: 21% (10/47), 53% (7/13), 45% (11/24) and 75% (6/8). Die multivariate Datenanalyse konnte Multiresistenz (adjusted HR 3.40 [95% CI 1.28-9.03], P=0.01) als einen unabhängigen Risikofaktor für erhöhte Mortalität feststellen. Zusammenfassung: Die Ergebnisse der Analyse heben die hohe Mortalität für Sepsis durch Pseudomonas aeruginosa hervor. Stämme mit mindestens zwei Resistenzen stellen den Hauptrisikofaktor für erhöhte Mortalität dar. Die Studie kann keine therapeutische Überlegenheit einer antimikrobiellen Kombinationstherapie gegenüber einer Monotherapie feststellen. Die Ergebnisse unterstützen die bisherige Beweislage für die Auswirkung von empirischer Antibiotikatherapie auf die Mortalität für Patienten mit einer Pseudomonas aeruginosa Sepsis und liefern wichtige Daten für das Verständnis einer rationalen Antibiotikaanwendung („Antibiotic Stewardship“)

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate´s phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.J.T.S. holds a research contract from the Fundación para la Formación e Investigación de los Profesionales de la Salud de Extremadura (FundeSalud), Instituto de Salud Carlos III. M.F.R. holds a clinical research contract “Juan Rodés” (JR14/00036) from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III

Incidência e resistência a antibióticos em bactérias implicadas nas infeções urinárias no distrito de Aveiro Norte (2011-2014)

Mestrado em MicrobiologiaThe urinary tract infection is the second most common infection in community and the most common nosocomial infection worldwide. Specific subpopulations are more likely to have UTI, such as, infants, pregnant women, elderly, diabetics, patients with urologic abnormalities, patients with catheters and immunodeficients. All the samples were collected at Centro Médico da Praça Lda on ambulatory system, located in São João da Madeira municipality, District of Aveiro north (Portugal) from June 2011 to June 2014. From 4270 analysed urine samples, 3561 (83%) were collected from women and only 709 (17%) were collected from men, in a range age from 0 to 104 years old. E. coli was (64%) the most frequent uropathogen, followed by Klebsiella spp (12%), Enterococcus spp (7%) and P. mirabilis (6%). From all samples, 1537 (37%) were multidrug resistant (MDR), 1099 were from women and 437 from men. The MDR uropathogens were resistant on average to a 6 antimicrobials and to a 5 antimicrobial classes of drugs. In general, men were more resistant to antimicrobials than women. According the results of this study, among the first line drugs recommended by EUA for empirical treatment of UTI the antimicrobials only nitrofurantoin is suitable for both sexes and ciprofloxacin may be only considered to treat women. From EAU recommended second line therapy, ampicillin is not appropriated to empirical treatment for both sexes, amoxicillin-clavulanic acid and trimethoprim-sulfamethoxazole should not be considered for men UTI empirical treatment, due the local high incidence of resistance. Thus, it is suggested imipenem and gentamicin as alternatives to treat both sexes.A infeção do trato urinário é a segunda infeção mais comum na comunidade e a mais comum no contexto hospitalar a nível mundial. As crianças, grávidas, idosos, diabéticos, pacientes com deformidades urológicas, cateterizados e imunodeficientes são considerados população de risco e por isso são mais propensos a desenvolver infeção do trato urinário. As amostras estudadas foram colhidas em regime de ambulatório no laboratório de análises clínicas, Centro Médico da Praça Lda, no município de São João da Madeira, distrito de Aveiro (Portugal), durante o período de estudo entre junho de 2011 a junho de 2014. E. coli (64%) foi a bactéria patogénica mais frequente, seguida da Klebsiella spp (12%), de Enterococcus spp (7%) e P. mirabilis (6%). Das 4270 urinas analisadas, 3561 (83%) foram colhidas em mulheres e apenas 709 (17%) em homens, num intervalo de idade entre 0 e os 104 anos. Desta amostra 1537 (37%) eram multirresistentes, entre elas 1099 foram colhidas de mulheres e 437 de homens. As bactérias patogénicas multirresistentes foram em média resistentes a 6 antibióticos e a 5 classes de antibióticos. Na generalidade os homens foram mais resistentes que as mulheres. Os resultados do estudo mostraram que dos antibióticos de primeira linha de tratamento apenas a nitrofurantoína é apropriado no tratamento empírico para ambos os sexos. Dos antibióticos sugeridos pela EAU como segunda linha de tratamento, a Amoxicilina - ácido clavulânico e o sulfametoxazole - trimetoprim pode ser considerado apenas para tratar mulheres, por fim, a ampicilina não é adequada para aos pacientes deste estudo. Deste modo, é sugerido como alternativa os antibióticos imipenem e gentamicina para o tratamento empírico de ambos os sexos

Strengthening antimicrobial resistance surveillance in Indonesia:Strategies for surveillance of uropathogens

Antimicrobial resistance (AMR) represents one of the most important threats to global health. Inappropriate use of antibiotics is a key driver of AMR. Surveillance is one important approach for tackling AMR, in order to: (1) inform empirical antibiotic therapy, (2) monitor trends in AMR and antibiotic use, and (3) inform policy at national and international levels. However, there are multiple challenges when implementing AMR surveillance, including cost, logistics, availability of relevant and timely information of AMR, and laboratory capacity. Novel approaches are thus needed that require minimum resources to produce high-quality and relevant surveillance data. Uropathogens are the most common bacteria causing infections in hospitals and in the community, and are commonly treated with empirical antibiotics. AMR in uropathogens is associated with increasing morbidity and mortality. This thesis assesses surveillance practices in the Asia-Pacific region, including Indonesia, and investigates the use of rapid threshold surveillance approaches, in particular Lot Quality Assurance Sampling (LQAS), for AMR surveillance among uropathogens. The research highlights the importance of unbiased population-based sampling in the out-patient setting, and the need for quality-assured laboratory processes. LQAS-based AMR surveillance should be considered when implementing surveillance for obtaining locally relevant AMR data

High dose versus low dose standardised cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection in healthy women : a double-blind randomized controlled trial

Introduction: Les infections urinaires (UTI) sont parmi les infections bactériennes les plus communes chez les femmes. Actuellement, les antibiotiques sont le traitement de choix pour la prévention des UTIs. Pourtant, les produits dérivés de la canneberge sont souvent utilisés avec peu d’évidence de leur efficacité. Notre objectif était d’évaluer l’efficacité d’un extrait de canneberge standardisé en proanthocyanidines de type A (PAC) sur la prévention des UTI à répétition. Méthodes: 145 femmes âgées de 18 ans et plus avec antécédents d’UTI à répétition, définie par ≥ 2 UTIs dans les derniers 6 mois ou ≥ 3 UTIs dans les derniers 12 mois, ont participé à notre essai clinique randomisé à double insu. Soixante-douze femmes ont reçu une dose optimale d’extrait de canneberge quantifié et standardisé en PACs (2 x 18,5 mg PACs par jour) et 73 ont reçu une dose contrôle (2 x 1 mg PACs par jour). L’issue principale était le nombre moyen de nouvelles UTIs symptomatiques chez les participantes durant une période d’intervention de 6 mois. Les issues secondaires étaient : 1) évaluer le nombre moyen d’UTI avec pyurie et avec confirmation microbiologique; 2) décrire les effets secondaires d’une dose quotidienne d’extrait de canneberge. Résultats: Sur la période de suivi de 6 mois, le risque d'UTIs symptomatiques n’était pas significativement différent entre les deux groupes (rapport de taux d’incidence 0,76, 95% IC 0,51-1,11 ; rapport de taux d’incidence ajusté pour l’âge 0,85, 95%IC 0,57-1,26). Parmi les participantes ayant eu moins de 5 UTIs dans l’année précédant leur participation, la prise de 2x18,5 mg était associée à une diminution des UTIs symptomatiques comparativement à une prise de 2x1 mg PACs (rapport de taux d’incidence ajusté pour l’âge 0,57,, 95%IC 0,33-0,99). Aucun effet secondaire majeur n’a été rapporté. Conclusion: La prise d’un extrait de canneberge en teneur élevée de proanthocyanidins n’a pas été associée à une réduction du taux d’incidence d'infections urinaires symptomatiques par rapport à un extrait de proanthocyanidines à faible dose. Nos résultats post-hoc suggèrent que la prise d’une dose de 2x18,5 mg PAC par jour pourrait prévenir les UTIs symptomatiques chez les femmes ayant moins de 5 UTIs par année.Background: Urinary tract infections (UTI) are amongst the most common bacterial infections affecting women. Although antibiotics are the treatment of choice for prevention of UTI, cranberry-derived products are often used by women to prevent UTIs, with limited evidence as to their efficacy. Our objective was to assess the efficacy of a cranberry extract capsule standardized in A-type linkage proanthocyanidins (PACs) for the prevention of recurrent UTI. Methods: 145 women aged 18 years or more with a history of recurrent UTI, defined as ≥ 2 UTIs in the past 6 months or ≥ 3 UTIs in the past 12 months were recruited in this randomized, controlled, double-blind clinical trial. Seventy-three women received an optimal dose of cranberry extract standardized in PACs (2 x 18.5 mg PACs daily) and 72 women received a control dose (2 x 1 mg PACs daily). The primary outcome for the trial was the mean number of new symptomatic UTIs in women during a 6-month intervention period. Secondary outcomes were: 1) To evaluate the mean number of new symptomatic UTIs with pyuria and with microbiological confirmation; 2) To describe the side effects of daily intake of cranberry extract. Results: No significant difference in the risk of UTI during the 24-week follow-up period was found between treatment groups (incidence rate ratio 0.75, 95%CI 0.51-1.11, age-adjusted incidence rate ratio 0.85, 95%CI 0.57-1.26). In women who experienced less than 5 UTIs in the year preceding enrolment, the daily consumption of 2x18.5 mg PACs was associated with a decrease in the risk of symptomatic UTIs reported compared to the control dose (age-adjusted incidence rate ratio 0.57, 95% confidence interval 0.33-0.99). No major side effects were reported. Conclusion: High dose twice daily proanthocyanidin extract was not associated with a reduction in the number of symptomatic urinary tract infections when compared to a low dose proanthocyanidin extract. Our post-hoc results reveal that this high dose of proanthocyanidins may have a preventive impact on symptomatic urinary tract infection recurrence in women who experienced less than 5 infections per year